Generation of a Protective T-Cell Response Following Coronavirus Infection of the Central Nervous System Is Not Dependent on IL-12/23 Signaling
| Autor: | Kimberly A. Shamberger, Mark Cunningham, Jill Carton, Heena Beck, Thomas E. Lane, William G. Glass, Katherine S. Held, Ted D. Petley, Patrick Branigan, Yevgeniya I. Orlovsky, Jacqueline Benson |
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| Rok vydání: | 2008 |
| Předmět: |
Central Nervous System
T-Lymphocytes Encephalomyelitis Immunology Central nervous system medicine.disease_cause Interleukin-23 Autoimmune Diseases Mice Mouse hepatitis virus Virology Interleukin 23 Demyelinating disease medicine Animals Coronavirus Murine hepatitis virus biology Experimental autoimmune encephalomyelitis Cellular Immunity medicine.disease biology.organism_classification Interleukin-12 medicine.anatomical_structure Viral replication Molecular Medicine Female Coronavirus Infections Demyelinating Diseases |
| Zdroj: | Viral Immunology |
| ISSN: | 1557-8976 0882-8245 |
| DOI: | 10.1089/vim.2008.0014 |
| Popis: | The functional role of IL-12 and IL-23 in host defense and disease following viral infection of the CNS was determined. Instillation of mouse hepatitis virus (MHV, a positive-strand RNA virus) into the CNS of mice results in acute encephalitis followed by a chronic immune-mediated demyelinating disease. Antibody-mediated blocking of either IL-23 (anti-IL-23p19) or IL-12 and IL-23 (anti-IL-12/23p40) signaling did not mute T-cell trafficking into the CNS or antiviral effector responses and mice were able to control viral replication within the brain. Therapeutic administration of either anti-IL-23p19 or anti-IL-12/23p40 to mice with viral-induced demyelination did not attenuate T-cell or macrophage infiltration into the CNS nor improve clinical disease or diminish white matter damage. In contrast, treatment of mice with anti-IL-12/23p40 or anti-IL-23p19 resulted in inhibition of the autoimmune model of demyelination, experimental autoimmune encephalomyelitis (EAE). These data indicate that (1) IL-12 and IL-23 signaling are dispensable in generating a protective T-cell response following CNS infection with MHV, and (2) IL-12 and IL-23 do not contribute to demyelination in a model independent of autoimmune T-cell–mediated pathology. Therefore, therapeutic targeting of IL-12 and/or IL-23 for the treatment of autoimmune diseases may offer unique advantages by reducing disease severity without muting protective responses following viral infection. |
| Databáze: | OpenAIRE |
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